Manage your subscription

Jumping for health

By Julie Clayton

“THE nucleus is where my passion is,” says immunologist David Schatz of Yale
University. “I love thinking about what happens in the nucleus and how those
chromosomes work.” In particular, he would like to understand how the white
blood cells of the immune system rearrange the DNA in their chromosomes to meet
new infectious challenges. Schatz’s work has already revealed how two key
enzymes help to generate the diversity needed by our immune systems to combat
disease. His finding may also inspire researchers in the fight against cancers
of the immune system, called lymphomas.

Our immune system can recognise huge numbers of different invaders. Each of
the millions of white blood cells has its own unique protein receptor on its
surface. In B and T cells, the genes that code for receptor proteins are made
from many DNA fragments that lie along their respective chromosomes. During a
cell’s development, these fragments can be shuffled around and recombined in
endlessly different ways to yield a plethora of different receptor proteins.
With this enormous variety there will always be some cells that can recognise
any invader and trigger an immune reaction.

In 1989, Schatz and Marjorie Oettinger, working in the lab of Nobel laureate
David Baltimore, discovered the enzymes RAG1 and RAG2, which are responsible for
this immune cell recombination. The enzymes recognise where the target fragments
reside and cut the DNA on either side. Other enzymes then paste these fragments
together to produce a new line-up of gene fragments, ready to dictate the
manufacture of a new receptor protein.